Effect of physical exercise on muscle strength in adults following bariatric surgery: A systematic review and meta-analysis of different muscle strength assessment tests

Individuals following bariatric surgery are considered at high risk for the development of sarcopenic obesity (excess fat mass, low muscle mass and low physical function), and exercise may play an important role in its prevention and treatment. We systematically reviewed 5 scientific databases (Embase, Medline, Scopus, SPORTDiscus, and Web of Science) and 2 grey literature databases (ProQuest and Google Scholar) for clinical trials that evaluated the effect of exercise on muscle strength in adults following bariatric surgery and conducted a separate meta-analysis for studies that used different muscle strength tests. Random-effect models, restricted maximum likelihood method and Hedges’ g were used. The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020152142). Fifteen studies were included (638 patients), none had a low risk of bias, and all were included in at least 1 of the 5 meta-analyses (repetition maximum [lower and upper limbs], sit-to-stand, dynamometer, and handgrip tests). Exercise interventions improved both upper (effect size, 0.71; 95% CI, 0.41–1.01; I2 = 0%) and lower (effect size, 1.37; 95% CI, 0.84–1.91; I2 = 46.14) limb muscle strength, as measured by repetition maximum tests. Results were similar for the sit-to-stand (effect size, 0.60; 95% CI, 0.20–1.01; I2 = 68.89%) and dynamometer (effect size, 0.46; 95% CI, 0.06–0.87; I2 = 31.03%), but not for the handgrip test (effect size, 0.11; 95% CI, -0.42–0.63; I2 = 73.27%). However, the certainty level of the meta-analyses was very low. Exercise with a resistance training component performed post bariatric surgery may improve muscle strength, which is related to sarcopenic obesity, functional capacity, and mortality risk, therefore should be included in the follow-up.


Introduction
Bariatric surgery (BS) can lead to severe energy and protein restriction or malabsorption, particularly in the first year postoperatively, culminating in fat-free mass (FFM) loss [1,2]. FFM is also associated with resting metabolic rate [3], longevity [4], and strength [5], which can be compromised during abrupt weight loss [6]. Individuals following BS are considered at high risk for the development of sarcopenic obesity (excess fat mass, low muscle mass and poor physical function) [7].
Regular physical activity is an important adjunct therapy following BS [8]. However, most individuals do not achieve minimum physical activity recommendations [9]. Previous metaanalyses have suggested that patients who perform exercise after BS demonstrate greater weight/fat loss and better aerobic capacity compared with sedentary patients [10,11]. Furthermore, including resistance exercises in addition to aerobic exercises improved the results [10].
Aerobic exercise training has historically been associated with improved metabolic regulation, cardiovascular function, and aerobic capacity; however, it may also be associated with muscle hypertrophy [12]. Resistance training promotes muscle strengthening and induces muscle hypertrophy in the general population [13]. Although muscle mass and strength are positively correlated, comorbidities such as obesity may affect this association, due to muscle deconditioning, inflammation, and fat infiltration into muscle [14]. Exercise performed post BS struggles to generate changes in lean mass and may only exhibits increase in muscle strength (MS) [11,15]. MS has a better prognostic value than FFM in predicting worsening disability [16]. Furthermore, MS has an independent inverse association with mortality risk [17].
Previous systematic reviews have addressed some of the effects of exercise on MS in the postoperative period following BS; however, most did not include a meta-analysis [10,18,19]. Bellicha et al. [11] were the first to publish a relevant meta-analysis; however, they combined the results of studies that evaluated MS with different tests and muscle groups. In many musculoskeletal conditions, optimal muscle function is important regarding quality of life and rehabilitation, and the maximal MS an individual can produce in different tasks should be known to design a proper rehabilitation program [20]. Each measurement test evaluates different MS features, therefore combining them as a single variable could decrease the inference power and limit appropriate conclusions.
Evaluating differences in MS according to specific muscle groups and strength tests may provide a deeper understanding of the association between physical exercise and MS. This may facilitate the development of optimal exercise interventions and MS assessment protocols for postoperative care after BS. Therefore, we systematically reviewed the effect of exercise on MS in individuals following BS and conducted a separate meta-analysis for studies that used different MS tests.
Clinical trials were included if they 1) evaluated adults who underwent BS (mostly Rouxen-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]) at any postoperative time point; 2) contained information about the type, frequency, and duration of exercise intervention; 3) evaluated MS (using any method); and 4) included a control group. Studies that exclusively evaluated specific populations with chronic diseases and exercise interventions administered in conjunction with an ergogenic resource were excluded. To reduce publication and retrieval bias, the search was not restricted by language, publication date, or publication status. This article does not contain any studies with human participants or animals performed by any of the authors.

Procedures
The search strategy was evaluated by an expert researcher using the Peer Review of Electronic Search Strategies (PRESS) checklist [22]. The PICO strategy was used for the research question construction and evidence search. Details of the search strategies adapted for the different databases are shown in S1 Table. Five scientific databases (Embase, Medline, Scopus, SPORTDiscus, and Web of Science) and 2 grey literature databases (ProQuest and Google Scholar) were systematically searched. Google Scholar was partially searched; only the first 200 relevant articles were screened. All databases were searched up to October 27, 2021. The Rayyan 1 software program was used to remove duplicate references before screening [23].
Study selection was conducted in 2 phases. In the first phase, 2 reviewers independently screened the titles and abstracts of the retrieved references. Studies that did not meet the eligibility criteria were excluded. In the second phase, the full texts of the articles identified in the first phase were independently assessed by the same reviewers. Disagreements regarding study eligibility were discussed between the 2 reviewers to reach a consensus; a third reviewer made a final decision when necessary. The reference lists of the included studies were also manually searched for relevant articles.
Data were independently extracted by 2 reviewers and cross-checked. Disagreements were resolved through discussion and, when necessary, a consensus was reached with the assistance of a third reviewer. The following variables were extracted from the included studies: country, study design, study aim, patient characteristics, BS type, postoperative time, intervention and control group protocols, strength measures, and outcomes/main results.
Authors were contacted by e-mail in cases where clarification was required or data of interest were missing. If no response was received within 2 weeks, a second e-mail was sent. The reviewers made a final decision if there was no response after another 15 days.
Risk of bias assessments were conducted independently by the 2 reviewers using the Joanna Briggs Institute critical appraisal tools for randomized controlled trials [24]. Any discrepancies were resolved by consensus; if necessary, a third reviewer served as the arbitrator. The instrument consists of 13 questions that evaluate the possibility of bias in the design, conduct, and analysis of each study. The possible answers are yes, no, unclear, and not applicable. An answer of "no" for any item meant that the study was not considered to have an overall low risk of bias. The risk of bias assessment was not used as a criterion for study eligibility.

Summary measures and data analysis
Outcome measurements (mean and standard deviation) for MS were extracted at baseline and follow-up for both the exercise and control groups. Meta-analyses were conducted using random-effects models and the restricted maximum likelihood method [25]. Differences in parameters between the control and intervention groups were estimated using Hedges' g and its 95% confidence interval (CI) [26].
Heterogeneity of treatment effects between studies was evaluated using the Chi-square method (p<0.10) and the I 2 statistic. Following the recommendations of the Cochrane Collaboration, heterogeneity was not considered important if I 2 was <40% [25]. To investigate parameters influencing heterogeneity, we performed subgroup analyses to evaluate the effects of assessing different muscle groups and the type of MS assessment. A sensitivity analysis was also performed to account for the type of intervention. Because of the small number of studies included in each meta-analysis, it was not possible to assess publication bias using meta-regression [25]. All statistical analyses were performed with Stata (version 16.1, Stata Corporation, College Station, TX) using the "meta" command.
Two reviewers independently evaluated the certainty of evidence from each meta-analysis with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach [27]. Disagreements were discussed between the 2 reviewers until they reached a consensus. In the GRADE approach, the certainty of evidence is rated as high, moderate, low, or very low by evaluating 5 domains (risk of bias, inconsistency, indirectness, imprecision, and publication bias). The GRADEpro GDT 2020 1 software program was used to prepare the summary of findings table, which included the downgrade justification for each level of certainty.
The total number of patients across all studies was 638; individual study sample sizes ranged from 13 [36] to 70 [38] patients. Patient age ranged from 18-65 years, and the majority of patients had a body mass index >30 kg/m 2 . Three studies only evaluated women [6,34,36].
Herring et al. [33] was excluded from the meta-analysis for the sit-to-stand test as they used a different test methodology. Galle et al.'s study [38] was also excluded because of a high level of heterogeneity that was attributed to the lack of a 30-or 60-second time limit and the performance of tests until exhaustion.
The 5 meta-analyses yielded a very low certainty of evidence according to the GRADE evaluation (S3 Table). None of the individual studies had a low risk of bias. Therefore, the included studies contributed more than 50% of the weight to the pooled estimate for each meta-analysis. For inconsistency, 2 meta-analyses demonstrated highly significant heterogeneity, whereas another 1 showed moderate non-significant heterogeneity. Regarding indirectness, all metaanalyses were downgraded 1 level due to a high degree of variability in the exercise protocols; 2 meta-analyses were affected by population heterogeneity, particularly concerning postoperative time. Regarding imprecision, none of the meta-analyses included the minimum sample size of 400 patients. Despite the estimate of treatment effect favoring the intervention in the handgrip meta-analysis, the 95% CI included the null value (S3 Table).
As none of the meta-analyses included more than 10 studies, Egger's test could not be used to assess publication bias. Therefore, we assessed publication bias by evaluating the search strategy and use of industry funding; the results indicated that none of the meta-analyses were affected by publication bias.

Discussion
Current evidence indicates that physical exercise interventions, especially with a resistance training component, may be effective in increasing MS in patients following BS [6, 28-36, 38, 40, 41]. Analysis of MS by the RM test showed that physical exercise was effective for both the upper and lower limbs. Similar results were found with the sit-to-stand and dynamometer tests but not with the handgrip test. Notably, all studies included in this systematic review were not appraised as having a low risk of bias, and the results of all 5 meta-analyses had very low levels of certainty. Despite the moderate effects, our results need to be considered in the context of the negative impact of BS on FFM and MS, with elevated risk for sarcopenic obesity.
Our findings are consistent with those of previous systematic reviews [10,11,18,19]. Nevertheless, we accounted for the use of different MS assessment methods, which focus on different muscle groups and types of strength. Additionally, our review included several recent studies that have not been incorporated in prior meta-analyses.
The general population is recommended to participate regularly in resistance training to increase MS. However, there are currently no specific guidelines for physical activity or exercise in individuals following BS, and existing training protocols vary widely in type, intensity, duration, and frequency [8].
A large national cohort study showed that obesity, low MS, and low aerobic fitness were independently associated with increased mortality [42], and even small changes in either upper or lower limb MS can affect the mortality risk [17]. Moreover, MS and aerobic fitness had interactive effects, thus demonstrating the need to promote both dimensions of physical fitness, especially for individuals with obesity [42]. The combination of resistance training with aerobic exercise, when compared with isolated aerobic exercise, was superior regarding weight loss, functional capacity, FFM, and MS after BS [32,43]. The following factors must be considered when assessing MS: muscle contraction type, measurement system, test equipment, pattern and range of motion, and loading scheme [44]. Isokinetic dynamometers are commonly used for MS assessment in the laboratory for the validation of other strength assessment measurements [45] and are used to evaluate isometric and isokinetic peak torque [46]. However, they are expensive and generally only evaluate a singlejoint muscle exercise; furthermore, the movement performed does not resemble that used in routine activities [47].
1RM and isometric tests are generally used for MS assessment in clinical settings. The 1RM is defined as the maximum weight that can be lifted once while maintaining the correct lifting technique [48]. The 1RM test has some advantages, such as allowing the evaluation of multijoint exercises making it better able to reflect dynamic muscle actions that are used in daily life; it is also widely used and cost-effective. However, populational studies can be time-consuming [49]. 1RM test reliability tends to be excellent, regardless of age, sex, body part assessed, and experience in resistance training [50]. The 1RM can also be predicted through 5-10 submaximal repetitions by equations that are exercise and population specific, which do not submit individuals to their maximum external loads; however, tests with more than 10 repetitions are not recommended [51].
Isometric strength tests, such as the handgrip test, are versatile, time-efficient, and strongly correlated with maximum dynamic strength during similar movement patterns [46,52]. However, they require specialized devices such as a tension gauge or force platform [44]. In this systematic review, the handgrip test was unable to detect the positive effects of exercise on MS in cases where effects could be detected by other assessment tests [28,29,41]. The sensitivity of a MS assessment test may be specific to the training program performed [44]. Exercise interventions with a resistance training component that included manual isometric exercises were able to increase MS measured with handgrip test in different clinical populations [43,53,54].
The sit-to-stand test assesses an individual's ability to independently get up from a chair. It has a good correlation with lower limb MS and the 6-minute walk test and is commonly used in the elderly, healthy young adults, and clinical populations [55][56][57]. Special attention is required when interpreting the results of the sit-to-stand test owing to methodological variations in the maximum number of repetitions performed within a 30-or 60-second time interval [58] and the time required to perform a predetermined number of repetitions (e.g., 5-10) [59]. This review has some limitations. First, our data were limited to a small number of clinical trials (with restrictive sample sizes), which limits the random-effects model interpretation. Second, none of the included studies had a low risk of bias, and all results generated by the metaanalyses had very low levels of certainty. Third, there was a high level of heterogeneity among the included studies due to differences in interventions. Thus, we were unable to assess the effect of various study characteristics on the observed estimates. Fourth, most of the studies focused on the early postoperative period, during which there is a large loss of weight, FFM, and absolute MS. Lastly, for the lower limbs' dynamometer meta-analysis, isokinetic and isometric data were pooled in the same analysis, due to limited number of studies, which did not allow separated investigations. However, even though they represent two different aspects of strength production [20], they are highly correlated [60,61], and were performed in similar devices.
The strengths of this review include the protocol registration in PROSPERO, a wide independently literature search following the PRESS recommendations, and the manual check of the reference lists. To ensure transparency of reporting, we adhered to the 2020 PRISMA guide [21], Cochrane handbook for performing meta-analyses [25], and GRADE [27] approach. Furthermore, we included trials with a wide range of characteristics to increase the generalizability of our results. To our knowledge, this is the first meta-analysis to evaluate the effect of exercise on MS assessed with different methodologies in individuals following BS.
In conclusion, physical exercise with a resistance training component performed after BS may improve MS, a variable closely related to sarcopenic obesity, functional disability and mortality risk, therefore it is essential to be performed as an adjuvant therapy in the postoperative follow-up care. Improvements in MS were observed when assessments were made with the RM (upper and lower limbs), sit-to-stand, and dynamometer tests, but not with handgrip test. Knowing in depth the MS assessment methods most used in research and in clinical practice helps the practitioner to choose the most appropriate method for the target population and purposes. Additional high-quality randomized clinical trials are required to determine the optimal exercise intervention protocol to improve MS for this population.